Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS4JKNQ)

DOT Name Tubulin-specific chaperone D (TBCD)
Synonyms Beta-tubulin cofactor D; tfcD; SSD-1; Tubulin-folding cofactor D
Gene Name TBCD
Related Disease
Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome ( )
Intellectual disability ( )
Paralysis ( )
Schizophrenia ( )
Spastic quadriplegic cerebral palsy ( )
Spinal muscular atrophy ( )
Spinal muscular atrophy, type 1 ( )
West syndrome ( )
Corneal dystrophy ( )
Isolated congenital microcephaly ( )
Microlissencephaly ( )
Respiratory failure ( )
Asthma ( )
UniProt ID
TBCD_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12612
Sequence
MALSDEPAAGGPEEEAEDETLAFGAALEAFGESAETRALLGRLREVHGGGAEREVALERF
RVIMDKYQEQPHLLDPHLEWMMNLLLDIVQDQTSPASLVHLAFKFLYIITKVRGYKTFLR
LFPHEVADVEPVLDLVTIQNPKDHEAWETRYMLLLWLSVTCLIPFDFSRLDGNLLTQPGQ
ARMSIMDRILQIAESYLIVSDKARDAAAVLVSRFITRPDVKQSKMAEFLDWSLCNLARSS
FQTMQGVITMDGTLQALAQIFKHGKREDCLPYAATVLRCLDGCRLPESNQTLLRKLGVKL
VQRLGLTFLKPKVAAWRYQRGCRSLAANLQLLTQGQSEQKPLILTEDDDEDDDVPEGVER
VIEQLLVGLKDKDTVVRWSAAKGIGRMAGRLPRALADDVVGSVLDCFSFQETDKAWHGGC
LALAELGRRGLLLPSRLVDVVAVILKALTYDEKRGACSVGTNVRDAACYVCWAFARAYEP
QELKPFVTAISSALVIAAVFDRDINCRRAASAAFQENVGRQGTFPHGIDILTTADYFAVG
NRSNCFLVISVFIAGFPEYTQPMIDHLVTMKISHWDGVIRELAARALHNLAQQAPEFSAT
QVFPRLLSMTLSPDLHMRHGSILACAEVAYALYKLAAQENRPVTDHLDEQAVQGLKQIHQ
QLYDRQLYRGLGGQLMRQAVCVLIEKLSLSKMPFRGDTVIDGWQWLINDTLRHLHLISSH
SRQQMKDAAVSALAALCSEYYMKEPGEADPAIQEELITQYLAELRNPEEMTRCGFSLALG
ALPGFLLKGRLQQVLTGLRAVTHTSPEDVSFAESRRDGLKAIARICQTVGVKAGAPDEAV
CGENVSQIYCALLGCMDDYTTDSRGDVGTWVRKAAMTSLMDLTLLLARSQPELIEAHTCE
RIMCCVAQQASEKIDRFRAHAASVFLTLLHFDSPPIPHVPHRGELEKLFPRSDVASVNWS
APSQAFPRITQLLGLPTYRYHVLLGLVVSLGGLTESTIRHSTQSLFEYMKGIQSDPQALG
SFSGTLLQIFEDNLLNERVSVPLLKTLDHVLTHGCFDIFTTEEDHPFAVKLLALCKKEIK
NSKDIQKLLSGIAVFCEMVQFPGDVRRQALLQLCLLLCHRFPLIRKTTASQVYETLLTYS
DVVGADVLDEVVTVLSDTAWDAELAVVREQRNRLCDLLGVPRPQLVPQPGAC
Function
Tubulin-folding protein implicated in the first step of the tubulin folding pathway and required for tubulin complex assembly. Involved in the regulation of microtubule polymerization or depolymerization, it modulates microtubule dynamics by capturing GTP-bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is regulated via its interaction with ARL2. Acts as a GTPase-activating protein (GAP) for ARL2. Induces microtubule disruption in absence of ARL2. Increases degradation of beta tubulin, when overexpressed in polarized cells. Promotes epithelial cell detachment, a process antagonized by ARL2. Induces tight adherens and tight junctions disassembly at the lateral cell membrane. Required for correct assembly and maintenance of the mitotic spindle, and proper progression of mitosis. Involved in neuron morphogenesis.
Tissue Specificity Ubiquitously expressed.
Reactome Pathway
Post-chaperonin tubulin folding pathway (R-HSA-389977 )

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome DISHPNJQ Strong Autosomal recessive [1]
Intellectual disability DISMBNXP Strong Biomarker [1]
Paralysis DISF9I3O Strong Biomarker [1]
Schizophrenia DISSRV2N Strong Genetic Variation [2]
Spastic quadriplegic cerebral palsy DISBJRHC Strong Biomarker [1]
Spinal muscular atrophy DISTLKOB Strong Biomarker [3]
Spinal muscular atrophy, type 1 DISYCWUG Strong Biomarker [3]
West syndrome DISLIAU9 Strong Biomarker [4]
Corneal dystrophy DISRDPA6 moderate Genetic Variation [5]
Isolated congenital microcephaly DISUXHZ6 moderate Biomarker [4]
Microlissencephaly DISUCKNT moderate Biomarker [4]
Respiratory failure DISVMYJO moderate Biomarker [4]
Asthma DISW9QNS Limited Genetic Variation [6]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Tubulin-specific chaperone D (TBCD). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Tubulin-specific chaperone D (TBCD). [12]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Tubulin-specific chaperone D (TBCD). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Tubulin-specific chaperone D (TBCD). [13]
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7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Tubulin-specific chaperone D (TBCD). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tubulin-specific chaperone D (TBCD). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Tubulin-specific chaperone D (TBCD). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Tubulin-specific chaperone D (TBCD). [11]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of Tubulin-specific chaperone D (TBCD). [14]
APR-246 DMNFADH Phase 2 APR-246 affects the expression of Tubulin-specific chaperone D (TBCD). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Tubulin-specific chaperone D (TBCD). [16]
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⏷ Show the Full List of 7 Drug(s)

References

1 Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy. Am J Hum Genet. 2016 Oct 6;99(4):962-973. doi: 10.1016/j.ajhg.2016.08.003. Epub 2016 Sep 22.
2 Common variants on 17q25 and gene-gene interactions conferring risk of schizophrenia in Han Chinese population and regulating gene expressions in human brain.Mol Psychiatry. 2016 Sep;21(9):1244-50. doi: 10.1038/mp.2015.204. Epub 2016 Jan 5.
3 TBCD may be a causal gene in progressive neurodegenerative encephalopathy with atypical infantile spinal muscular atrophy.J Hum Genet. 2017 Apr;62(4):473-480. doi: 10.1038/jhg.2016.149. Epub 2016 Dec 8.
4 Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.Am J Hum Genet. 2016 Oct 6;99(4):950-961. doi: 10.1016/j.ajhg.2016.08.005. Epub 2016 Sep 22.
5 Clinical outcome of eight BIGH3-linked corneal dystrophies.Ophthalmology. 2002 Apr;109(4):793-7. doi: 10.1016/s0161-6420(01)01025-9.
6 Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts.J Allergy Clin Immunol. 2015 Nov;136(5):1240-6.e1-8. doi: 10.1016/j.jaci.2015.04.014. Epub 2015 May 27.
7 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
8 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
12 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
13 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
14 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
15 Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
16 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.